1. Field of the Invention
The present invention relates to a novel obovatol derivative or a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition for the prevention and treatment of cancer comprising the same as an active ingredient.
2. Description of the Related Art
With the development of civilization, the incidence of cancer has increased. The treatment of cancer is, for the most part, dependent on surgical therapy, radiation therapy and chemical therapy, with 40 anticancer agents showing strong cytotoxicity. However, because the application of these therapies is limited to cancer patients in early stages, or to certain types of cancers, cancer morbidity remains on an increasing trend.
In order to differentiate malignant tumors from benign ones, they should show malignant properties including cell growth promotion and invasion into adjacent tissues, and something that overcomes growth control signals from adjacent tissues is another criterion. Signaling pathways in normal cells comprise only growth promoting signals, but also convey growth-controlling messages from the outer surface deep into the nucleus. In cancer cells, however, signaling chains between cell growth inhibitory factors are loosened or broken. In addition, cancer cells even neglect the signals induced from potential inhibitory factors present on the surface thereof. In many cancer cells, a series of important inhibitory factors induced by cancer suppressor genes are lost or inactivated (Bruce A. J. Ponder, Nature, 411, 336-341, 2001).
Taken together, recent study results demonstrate that it is the molecular apparatus, known as the cell cycle clock, present in the nucleus that is ultimately affected by cell growth factors and growth inhibitory factors. All cancer cells undergo cell division at very high rates without the ability to regulate the cell cycle. In normal cells, all of the signals transferred thereinto are collectively regulated to thus determine the phase of the cell cycle to which each cell progresses. If a decision is made to conduct cell division, the cell cycle starts to work (Gerard I. Evan and Karen H. Vousden. Nature, 411, 342-348, 2001).
Two mechanisms are described above for regulating the growth of normal cells to suppress cancer generation. That is, they are to suppress cell growth factors or activate cell growth inhibitory factors. Despite the normal operation of the two regulating mechanisms, cells may be activated by themselves, or may replicate continuously regardless of external cell division stop signals so as to finally progress into cancer. Further, excessive genetic mutations within cells may incite cells to become cancerous in spite of all body defense functions.
Each human cell has a self-destruction function which starts to work when its fundamental constituents are damaged or its regulation system is not controlled. This phenomenon is called apoptosis. For example, damage to nuclear genes may induce programmed cell death. Further, many research groups have recently reported that the functional loss of tumor suppressor genes within cells as well as the expression of oncogenes induce apoptosis. The destruction of damaged cells is disadvantageous to the cells themselves, but is very useful for the body in its entirety. The destruction of cells in which oncogenic modification occurs functions to remove the potential risk of cancer. On rare occasions, if they do not experience cell death, genetically modified cells become cancerous (Andy Catherine Denicourt and Steven F. Dowdy, Science, 305, 1411-1413, 2004).
Ongoing cancer cells have tactics for avoiding cell death. The tumor suppressor factor p53 has an anti-cancer mechanism for inducing cells to destroy themselves. The cells in which this protein is inactivated have weakened self-destruction functions. Additionally, cancer cells produce the Bcl-2 protein in a large amount to avoid cell death. Recent studies have disclosed that interfering with cell death not only causes the spread of tumors, but also induces the resistance of tumor cells to chemicals, resulting in danger to cancer patients. Over the years, it has been believed that radiotherapy and various chemical therapies directly kill malignant cells by destroying a wide range of their genes. Nonetheless, cancer cells have the ability to avoid cell death and become resistant to cancer drugs. These research results suggest that radiation and chemical therapies capable of inducing apoptosis, if developed, may be effective weapons against cancer (John C. Reed, Nature Review Drug Discovery 1, 111-121, 2002).
Apoptosis-inducing materials can be found in the prior art. For example, Korean Patent Publication No. 2006-0000241 discloses a twin compound, synthesized through the pharmaceutical association of an anticancer drug with DMNQ, which acts specifically on human cancer cell lines A549, HT-1080, SK-OV-3 and U937 and can induce apoptosis in two p53-mutated kinds of the human pulmonary epithelial cell line A549.
Korean Patent No. 426450 teaches an anti-cancer composition comprising as active ingredients citric acid, albumin and zinc in pharmaceutically effective amounts in combination with a pharmaceutically acceptable carrier or diluent.
Korean Patent No. 548743 describes a novel inhibitor F-3-2-5, isolated from a soil actinomycetes culture, capable of inducing apoptosis in cancer cells, a preparation method thereof, and its use in anti-cancer agents.
Korean Patent No. 799266 discloses a composition for the prevention and treatment of cancer comprising widdrol, isolated from a Juniperus chinensis extract, as an active ingredient.
As such, a lot of effort has been made in organic synthesis and natural material fields to develop apoptosis-inducing materials.
However, there is still a need for anticancer materials that are harmless to the human body and highly effectively exert growth regulation and apoptosis on cancer cells without side effects.